JPH0465059B2 - - Google Patents

Description

[Detailed description of the invention]

<Industrial Application Field> The present invention relates to N-substituted acrylamides or methacrylamides [hereinafter referred to as N-substituted (meth)acrylamides]. ] related to the manufacturing method. More specifically, the present invention comprises a primary or secondary amine or a salt thereof and an alkali metal hydroxide or alkali metal salt in a two-phase mixed solvent of water and an organic solvent that is substantially immiscible with water. The general formula () is dissolved or dispersed in advance and then added to the mixture.

[Formula] (wherein R represents a hydrogen atom or a methyl group, and X represents a chlorine atom or a bromine atom) is added intermittently or continuously to This is a method for producing N-substituted acrylamide or methacrylamide, which comprises reacting with a primary or secondary amine or a salt thereof. The N-substituted (meth)acrylamides provided by the present invention can be polymerized by themselves or copolymerized with other polymerizable vinyl monomers to produce heat-responsive polymeric materials, moisture-controlling materials, etc. It is expected to be used as a variety of functional polymer materials such as moisture-permeable polymer materials, biocompatible polymer materials, and polymerizable polymer deterioration inhibitors, and has a wide range of applications. Furthermore, by quaternizing (meth)acrylamides with substituted amino groups, they become cationic monomers, and their polymers can be used as polymer flocculants, adhesives, papermaking agents, ion exchange resins, etc. Monomers having two or more (meth)acrylamide groups in the molecule can be used as crosslinking agents, curing agents, etc. <Prior art> Conventionally known methods for synthesizing N-substituted (meth)acrylamides include, for example, using an aqueous sodium hydroxide solution as a reaction aid in the reaction of (meth)acrylic acid chloride with alkylamines. Dropwise reaction method (US Pat. No. 2,311,548): N-(3-dimethylaminopropyl)acrylamide is produced by using an aqueous sodium hydroxide solution as a reaction aid in the reaction of acrylic acid chloride and dimethylaminopropylamine. (U.S. Pat. No. 2,595,907)
No.); A method in which a trialkylamine or the amine itself as a reaction substrate is used as a reaction aid in the reaction of (meth)acrylic acid chloride with amines [US Pat. No. 3,285,886, J.Org.Chem. 46 . 2182
(1981), Zhur.Obshchei Khim., 27 2239
(1957)]; Method of reacting (meth)acrylic acid and amines in the gas phase (U.S. Pat. No. 2,719,177;
No. 2719178); method of synthesis by reaction of alkyl (meth)acrylate with amines (U.S. Patent No. 2719178);
No. 2451436, No. 3878247, No. 4251461, No. 4267372, No. 4287363, JP 54-138513
No., No. 56-100749, No. 131555, No. 13155, No. 1983
No. 57-42661, No. 58-949), etc. However, in the method described in the above literature using (meth)acrylic acid chloride, it is difficult to adjust the dropping rate of the sodium hydroxide aqueous solution and (meth)acrylic acid chloride and control the reaction temperature, and it is difficult to quickly remove the generated hydrogen chloride. However, hydrochloric acid adducts and Michael adducts are produced, resulting in lower yields and purity, and the types of amines that can be used are also limited.
Particularly in reactions with dialkylamines and dialkylaminoalkylamines, there is the problem of by-product Michael adducts, and if a water-soluble product is obtained, it is easy to isolate and purify the product from the reaction product. Instead, they usually have to be purified by distillation, but this has the disadvantage that polymerization of the product is particularly likely to occur, resulting in an unavoidable reduction in yield. On the other hand, there have been no reports on the reaction of amines with salts. Furthermore, in the method described in the above-mentioned literature in which trialkylamine or the amine itself as a reaction substrate is used as a reaction aid, not only does the problem of Michael adduct by-product occur, but also the hydrochloride of the amine produced from the reaction product is There is a drawback that the operation becomes complicated due to the removal. In the method described in the above literature, in which (meth)acrylic acid and amine are reacted in the gas phase, not only the reaction takes place in two stages, but also the problems of formation and polymerization of Michael adducts are unavoidable, as well as high boiling point or solid state. The disadvantage is that it is difficult to react with amines. The method described in the above-mentioned literature, which involves the reaction of an alkyl (meth)acrylate with an amine, has the disadvantage that a reduction in yield due to by-products of Michael adducts and polymerization is unavoidable. <Problems to be Solved by the Present Invention> The present invention is an industrial method for obtaining N-substituted (meth)acrylamides in high yield while avoiding the above-mentioned Michael adducts and the reduction in yield due to polymerization during reaction and purification. The purpose of this invention is to provide a production method that is advantageous in terms of production efficiency. <Means and effects for solving the problems> In order to solve the above-mentioned problems, the present inventors have intensively studied methods for producing N-substituted (meth)acrylamides. When producing N-substituted (meth)acrylamides by reacting (meth)acrylic acid halides with amines, it is known that an aqueous solution of an alkali metal hydroxide or an organic solvent that is substantially immiscible with water is used. There is. However, (meth)acrylic acid halide,
We found that the yield and purity vary considerably depending on the method and order of addition of the amine, aqueous alkali solution, and organic solvent into the system.As a result of detailed investigation, we found that primary or secondary amines or their salts and alkali A metal hydroxide or an alkali metal salt is dissolved or dispersed in advance in a two-phase mixed solvent of water and an organic solvent that is substantially immiscible with water, and then the general formula () is added to the mixture.

[Formula] (wherein R represents a hydrogen atom or a methyl group, and X represents a chlorine atom or a bromine atom) is added intermittently or continuously to The present invention was completed by discovering that N-substituted (meth)acrylamides can be easily produced in high yield and purity by reacting with primary or secondary amines or their salts. Examples of the (meth)acrylic acid halide represented by the general formula () used in the present invention include acrylic acid chloride, acrylic acid bromide, methacrylic acid chloride, and methacrylic acid bromide. The amount of the (meth)acrylic acid halide used is in the range of 0.25 to 2.0 equivalents, preferably 0.5 to 1.5 equivalents, based on the sum of the number of _-NH2 groups or >NH groups in the amine compound. If the amount is less than 0.25 equivalent, the conversion rate will decrease and a large amount of unreacted amine compound will remain in the reaction system. If the amount is more than 2.0 equivalents, it is not only economically disadvantageous, but also the post-reaction treatment becomes complicated. The primary or secondary amines or their salts used in the present invention include aliphatic primary amines such as methylamine, butylamine, octadecylamine, and 2-methylthioethylamine, amines such as cysteamine hydrochloride, and cysteamine sulfate. salts of dimethylamine, diethylamine, aliphatic secondary amines such as ethyleneimine, alkylene diamines such as ethylenediamine and trimethylenediamine, 2,2-dimethylthiazolidine, 4-amino-2,2,6,6 - cyclic amines such as tetramethylpiperidine, piperidine, piperazine, morpholine, 2-dimethylaminoethylamine, 2-diethylaminoethylamine,
3-dimethylamino-n-propylamine, 3-
dialkylaminoalkylamines such as diethylamino-n-propylamine, 2-[(2-dimethylaminoethyl)amino]ethylamine, 3
- Triamines such as [(3-dimethylamino]-n-propyl)amino-n-propylamine or their homologues, tetraamines, aniline, N-methylaniline, α-naphthylamine, p-phenylenediamine , p-N,N-dimethylphenylenediamine, 2-aminobenzophenone, and aromatic amines such as 2-aminoacetophenone. The alkali metal hydroxides or alkali metal salts used in the present invention include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate,
Examples include sodium hydrogen carbonate and potassium hydrogen carbonate. The amount of the alkali metal hydroxide or alkali metal salt used can be selected from the range of 0.25 to 3.0 equivalents, preferably 0.55 to 1.6 equivalents based on the sum of the numbers of -NH ₂ groups and >NH groups of the amine compound. It is equivalent. Amounts less than 0.25 equivalents will reduce the yield of the product, while amounts greater than 3.0 equivalents will only be economically disadvantageous. When a salt of an amine is used, in addition to the amounts mentioned above, an equivalent amount of alkali metal hydroxide or alkali metal salt is used to neutralize the salt. The organic solvent used in the present invention includes:
Preferably, it is stable under the reaction conditions, is substantially insoluble in water, and dissolves the reaction product well. for example,
Examples include aliphatic hydrocarbons such as pentane, hexane, and heptane; aromatic hydrocarbons such as benzene, toluene, and xylene; and halogen compounds such as carbon tetrachloride, chloroform, and dichloromethane. The above organic solvents may be used alone or in a mixture of two or more. The organic solvent/water volume ratio is preferably 0.25 or more, more preferably 1 or more.
When the above-mentioned volume ratio is smaller than 0.25, the amount of the product eluted into the aqueous layer increases and the isolation yield decreases.
When the above-mentioned volume ratio is 1 or more, less product is eluted into the aqueous layer, and the decrease in isolation yield is small. The use of mixed solvents may result in the reaction products not being purified by distillation or
Otherwise, it works particularly advantageously when this is not possible. The reaction temperature is -10 to 60°C, preferably 0 to 40°C. At temperatures lower than -10℃, the reaction is slow;
At temperatures higher than 60°C, side reactions such as Michael addition reactions and polymerization reactions tend to occur, so preferably,
Although it is not necessarily essential to have a polymerization inhibitor present in the reaction system, p-methoxyphenol, hydroquinone, phenothiazine, cuprous chloride, chloranil, p-nitrobenzoic acid, which are generally known as polymerization inhibitors, It is preferable to add 2,5-dichloro-p-benzoquinone or the like to the reaction system. Embodiments of the separation and purification of the N-substituted (meth)acrylamides obtained in the present invention will be described below, but these embodiments are not intended to limit the present invention. Generally, after the reaction, salts are removed as an aqueous solution by separating the reaction mixture, and then the organic solvent is removed by distillation, and if necessary, N-substitution is carried out by further distillation or recrystallization. (Meth)acrylamides can be separated and purified. <Effects of the Invention> According to the method of the present invention, by using an inexpensive alkali metal hydroxide or alkali metal salt in a mixed solvent of water and an organic solvent, the reaction proceeds and is completed quickly, and after the reaction, N-substitution (meth) of the target product in high yield and purity with a simple operation of liquid separation.
Acrylamides are obtained. EXAMPLES Hereinafter, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples. Example 1 Dimethylamine 50% in a 2 capacity flask equipped with a stirrer, addition funnel, reflux condenser and thermometer.
200g (2.218mol) aqueous solution, sodium hydroxide
88.7g (2.218mol), 524ml water, dichloromethane
288 ml and 35 mg of p-methoxyphenol were charged and the internal temperature was cooled to 10°C or less. While stirring, 220.3 g (2.107 mol) of methacrylic acid chloride was added dropwise over 4 hours. The internal temperature was kept below 10°C during the reaction. After the reaction, stirring was continued for an additional 1.5 hours to complete the reaction. After the reaction was completed, the reaction solution was separated, and the organic layer of the reaction solution was dried over anhydrous sodium sulfate, and then the sodium sulfate was removed by filtration. Next, dichloromethane was distilled off under reduced pressure, and then distilled under reduced pressure (64℃/
10 torr) to obtain 227.2 g (2.008 mol) of N,N-dimethylmethacrylamide. The yield based on the starting methacrylic acid chloride was 95.3%. Example 2 73.1 g of diethylamine was placed in the same apparatus as in Example 1.
(1.000 mol), sodium hydroxide 40.0 g (1.000 mol), water 280 ml, dichloromethane 250 ml, phenothiazine 15 mg, and acrylic acid chloride 86.0 g (0.950 mol) instead of methacrylic acid chloride.
The same operation as in Example 1 was performed except that . 102.7 g (0.807 mol) of N,N-diethylacrylamide was obtained by vacuum distillation (79° C./10 torr). The yield based on the starting acrylic acid chloride is 84.9
It was %. Comparative Example 1 Diethylamine was added to a 500 ml flask equipped with a stirrer, addition funnel, reflux condenser and thermometer.
73.1g (1.000mol), diethyl ether 200ml,
0.100 g of hydroquinone was charged, and the internal temperature was cooled to 10°C or less. While stirring, 90.5 g (1.000 mol) of acrylic acid chloride and a solution of 40.0 g (1.000 mol) sodium hydroxide dissolved in 100 ml of water were simultaneously added dropwise over 2 hours. During the dropping, the internal temperature was kept below 15°C. After the dropwise addition was completed, stirring was continued for an additional hour. After the reaction is completed, the reaction solution is separated, the organic layer is washed twice with 100 ml of 0.2% sodium hydroxide aqueous solution, then washed with 25 ml of water, and the aqueous layer is washed with 40 ml of diethyl ether.
Extracted in ml. The washed organic layer and extracted ether layer were combined and dried over magnesium sulfate, and then the ether was distilled off under reduced pressure. Then distilled under reduced pressure to obtain N,N
-diethylacrylamide (boiling point 79℃/10torr)
63.5g (yield 49.9%) was obtained. Examples 3 to 8 In the same manner as in Example 1, the N-
Substituted amides were synthesized. The results are shown in Table-1.

[Table] Example 9 In a 300 ml flask equipped with a stirrer, dropping funnel, reflux condenser and thermometer, 17.6 g (0.200 mol) of 2-dimethylaminoethylamine, 8.80 g (0.220 mol) of sodium hydroxide, p- Nitrobenzoic acid
4.7 mg, 13.2 ml of water, and 132 ml of dichloromethane were charged, and the internal temperature was cooled to 10°C. Add 22.0 g (0.210 mol) of methacrylic acid chloride to this while stirring.
was added dropwise over 120 minutes. The internal temperature was kept below 20°C during the reaction. After the reaction was completed, the reaction solution was separated. Anhydrous sodium sulfate was added to the dichloromethane layer obtained by liquid separation, and after drying, the sodium sulfate was removed by filtration. Next, dichloromethane was distilled off under reduced pressure to give N-
(2-dimethylaminoethyl)methacrylamide
28.5g (0.182mol: yield 91.2%) was obtained. Example 10 Into the same apparatus as in Example 9, 17.6 g (0.200 mol) of 2-dimethylaminoethylamine, 8.40 g (0.210 mol) of sodium hydroxide, 7.8 mg of p-methoxyphenol, 160 ml of water, and 160 ml of dichloromethane were charged. The temperature was cooled to 10°C. Add 22.0 g of methacrylic acid chloride to this while stirring.
(0.210 mol) was added dropwise over 120 minutes. The internal temperature was kept below 20°C during the reaction. After the reaction was completed, the reaction solution was separated. Anhydrous sodium sulfate was added to the dichloromethane layer obtained by liquid separation, and after drying, the sodium sulfate was removed by filtration. Next, dichloromethane was distilled off under reduced pressure to obtain 24.2 g (0.155 mol: yield 77.3%) of N-(2-dimethylaminoethyl) methacrylamide. Examples 11 to 16 Into the same apparatus as in Example 9, the predetermined amounts of an amine compound, alkali metal hydroxide, polymerization inhibitor, water, and organic solvent shown in Table 2 were charged, and the internal temperature was maintained while stirring.
Cooled to 10°C. A predetermined amount of (meth)acrylic acid halide was added dropwise to this mixture over 120 minutes while stirring.
The internal temperature was maintained at 20°C during the reaction. After the reaction was completed, the reaction mixture was treated in the same manner as in Example 9 to obtain an N-substituted (meth)acrylamide compound. Table 2 of the results
It was shown to.

[Table] Example 17 279.4 g (3.000 mol) of aniline and 540 g of dichloromethane were placed in a 3-capacity glass flask equipped with a stirrer, thermometer, Dimroth condenser, and dropping funnel.
ml, sodium hydroxide 120.0g (3.000mol), water
1080 ml and 28 mg of p-methoxyphenol were charged in advance. While stirring vigorously, the system
Keep below ℃ methacrylic acid chloride 313.5g
(3.000 mol) was added over 100 minutes. After the dropwise addition was completed, stirring was continued for an additional 30 minutes, and the mixture was separated into two phases. The obtained organic layer was washed with dilute hydrochloric acid, water, and a 5% by weight aqueous sodium carbonate solution, and then washed repeatedly with water until the aqueous layer became neutral. After drying the obtained organic layer over anhydrous sodium sulfate, dichloromethane in the organic layer was distilled off and N-phenylmethacrylamide was extracted.
465.5g (yield 96.2%) was obtained. Examples 18-21 In the same manner as in Example 17, N-substituted amides of acrylic acid or methacrylic acid were synthesized by reacting acrylic acid or methacrylic acid chloride with an amine compound. The results are shown in Table-3.

[Table] Example 22 300 with stirrer, thermometer and dropping funnel
In a ml flask, add 120 ml of chloroform, 10.0 g (50.7 mmol) of 2-aminobenzophenone, and 15 ml of water.
ml and 5.54 g (66.0 mmol) of sodium hydrogen carbonate were charged, and 6.72 g (64.3 mmol) of methacrylic acid chloride was added dropwise over 75 minutes while maintaining the temperature in the reaction system at 2 to 4°C. After completion of the dropwise addition, stirring was continued for 3 hours while maintaining the temperature in the reaction system at 4 to 7°C to complete the reaction. After the reaction is complete, add 35ml to the reaction system.
was added and stirred, and then the liquid was separated. After washing the organic layer of the reaction solution twice with 50 ml of 1.6% sodium carbonate aqueous solution,
Washed twice with 100 ml of water. After the solvent in this organic layer was distilled off under reduced pressure, it was dried under reduced pressure to obtain 12.5 g (47.1 mmol) of N-methacryloyl-2-amino-benzophenone. The yield was 92.9% based on the 2-aminobenzophenone used. The purity was determined to be 99.6% by high performance liquid chromatography (using an ODS column). Examples 23 to 25 In the same manner as in Example 22, N-substituted amides of (meth)acrylic acid were synthesized by reacting (meth)acrylic acid chloride with an amine compound. The results are shown in Table-4.

【table】

Claims (1)

[Claims] 1. A primary or secondary amine or a salt thereof and an alkali metal hydroxide or an alkali metal salt are prepared in advance in a two-phase mixed solvent of water and an organic solvent that is substantially immiscible with water. dissolved or dispersed, and then poured into the mixture with the general formula () [formula] (wherein R represents a hydrogen atom or a methyl group,
represents a chlorine atom or a bromine atom. N-substituted acrylamide or methacrylamide, which is characterized in that acrylic acid halide or methacrylic acid halide shown in ) is added intermittently or continuously to react with the primary or secondary amine or a salt thereof. manufacturing method.